3+2] cycloaddition reactions of cyclopropyl imines with enones

A nickel-catalyzed [3+2] cycloaddition of cyclopropyl aldimines and enones has been developed. The process provides direct access to trisubstituted cyclopentanes, and the scope exceeds that of the corresponding reactions involving cyclopropyl ketones. A basis for the improved performance of cyclopropyl aldimines compared with cyclopropyl ketones is provided.     

Cyclopropyl-substituted pyrylium salts

The previously unknown 2,4,6-trisubstituted pyrylium salts 1-4 , carrying cyclopropyl and methyl or phenyl substituents in the same molecule, and 5-8 , substituted with isopropyl groups instead of cyclopropyl, were synthesized as perchlorates. The electronic spectra and the C-13 nmr spectra of the two groups of compounds were compared. A cyclopropyl group has a batochromic effect on the electronic spectrum roughly half that exerted by a phenyl; replacement of an alkyl by a cyclopropyl shifts the highest wavelength absorption band by about 20 nm. Presence of phenyl substituents reduces the batochromic effects of cyclopropyl substituents. The effects of both cyclopropyl and phenyl substituents on the electronic spectra are smaller for pyrylium than for tropylium. The nmr signals for all the ring carbons are shifted upfield upon replacement of isopropyl by cyclopropyl; in particular, the effect of substituents in position 2 upon the chemical shift of C(4) indicates that the electron-releasing effect varies in the series alkyl < phenyl < cyclopropyl, in agreement with the findings for 2,6-disubstituted pyrylium salts. The difference between the chemical shifts for the methine and methylene carbons of the three-membered ring is a function of the electron demand of the cationic heterocycle.     

环丙基甲基酮的合成研究进展

环丙基甲基酮是合成环丙氟哌酸类广谱抗菌药物和抗艾滋特效药依法韦仑的重要中间体,在医药、化工及农林等领域均有广泛应用。环丙基甲基酮的合成方法大致分为4类,分别以酮类、酯类、醇类及呋喃有机物为原料,在一定条件下生成环丙基甲基酮粗品,经萃取及精馏得到环丙基甲基酮纯品。本文综述了环丙基甲基酮的合成研究进展。     

Cyclopropyl organyl sulfides

Conclusions Three methods were developed for the synthesis of cyclopropyl organyl sulfides, which are based on the reaction of cyclopropyl halides with either thiols or alkali metal thiolates in a superbasic medium, the reaction of cyclopropyllithium with diorganyl disulfides, and the reaction of cyclopropyl alkyl sulfides with lithium in liquid ammonia and subsequent reaction with organic bromo derivatives. In contrast, the cleavage of cyclopropyl aryl sulfides leads to the formation of lithium arylthiolates.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 1664–1667, July, 1983.     

On the regioselectivity of the Ru-catalyzed intramolecular [5 + 2] cycloaddition

The influence of substituents on which cyclopropyl bond cleaves in the cycloisomerization of cyclopropylenynes catalyzed by CpRu(N&tbd1;CCH(3))(3)(+)PF(6)(-) is compared to the corresponding Rh-catalyzed reaction. With the trans cyclopropyl substrates, the bond energy of the cleaving bond appears to be an important factor. With cis cyclopropyl substrates, steric effects appear to dominate.     

Density function studies on the PtCl2‐catalyzed asymmetric cycloisomerization reaction of hydroxylated enynes

The PtCl₂‐catalyzed asymmetric cycloisomerization reaction of hydroxylated enynes was studied using density functional theory (DFT). All structures have been optimized completely at the B3LYP/6‐311G(d,p) level. As shown, the cycloisomerization reaction is exothermic. The cycloisomerization reaction mainly undergoes the formation of catalyst‐hydroxylated enzyme coordination, the asymmetric cyclopropyl platinum carbene, catalyst–cyclopropyl enol coordination, and catalyst–cyclopropyl ketone coordination. The chirality‐limiting step for the asymmetric cycloisomerization reaction is the formation of the asymmetric cyclopropyl platinum carbene, and the rate‐determining step for this reaction is the formation of the catalyst–cyclopropyl ketone coordination. The dominant products predicted theoretically are (R,S) ‐syn_5a, in agreement with the experiment. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Oxygen acidity of ring methoxylated 1,1-diarylalkanol radical cations bearing alpha-cyclopropyl groups. The competition between O-neophyl shift and C-cyclopropyl beta-scission in the intermediate 1,1-diarylalkoxyl radicals

A product and time-resolved kinetic study on the reactivity of the radical cations generated from cyclopropyl(4-methoxyphenyl)phenylmethanol (1) and cyclopropyl[bis(4-methoxyphenyl)]methanol (2) has been carried out in aqueous solution. In acidic solution, 1*+ and 2*+ display very low reactivities toward fragmentation, consistent with the presence of groups at Calpha (aryl and cyclopropyl) that after Calpha-Cbeta bond cleavage would produce relatively unstable carbon-centered radicals. In basic solution, 1*+ and 2*+ display oxygen acidity, undergoing -OH-induced deprotonation from the alpha-OH group, leading to the corresponding 1,1-diarylalkoxyl radicals 1r* and 2r*, respectively, as directly observed by time-resolved spectroscopy. The product distributions observed in the reactions of 1*+ and 2*+ under these conditions (cyclopropyl phenyl ketone, cyclopropyl(4-methoxyphenyl) ketone, and 4-methoxybenzophenone from 1*+; cyclopropyl(4-methoxyphenyl) ketone and 4,4'-dimethoxybenzophenone from 2*+) have been rationalized in terms of a water-induced competition between O-neophyl shift and C-cyclopropyl beta-scission in the intermediate 1,1-diarylalkoxyl radicals 1r* and 2r*.     

Dimerization of cyclopropyl ketones and crossed reactions of cyclopropyl ketones with enones as an entry to five-membered rings

An unexpected dimerization of cyclopropyl ketones was observed, and analysis of the reaction pathway led to development of a synthetically useful crossed reaction between cyclopropyl ketones and enones to afford densely functionalized cyclopentane products.     

Syntheses of Some Oyclopopxl Conjugated 1, 2-Diketojjes

A very recent publication by Guillaud, Pierre and Arnaud ¹ on the preparation and reactivity in basic media of some cyclopropyl conjugated 1,2-diketones prompted us to report our synthetic results in the same field. In connection with our interest in cyclopropyl conjugated carbonyl systeams way of preparing cyclopropyl conjugated 1,2-diketones is by oxidation of aither compound (I)or (II) with selenium dioxide.     

环丙烷基三甲基硅醚类化合物的脱硅基及酯化反应的研究

环丙烷基硅醚在卤化锌的作用下能够与硅胶反庆生成环丙基醇。研究了环丙烷基硅醚在卤化锌作用下与酰氯发生的酯化反应,发现在配位性较弱的溶剂二氯甲烷中,可得到比在乙醚中更高的产率。此外,采用一锅煮的方法,从烯醇硅醚出发,经过环丙化反应、酯化反应,以较好的产率合成了环丙基酯。     

Divergent synthesis of fully substituted isoxazoles and spiro-fused pyrazolin-5-ones from cyclopropyl oximes

Efficient and divergent synthesis of fully substituted isoxazoles and spiro-fused pyrazolin-5-ones is developed from cyclopropyl oximes based on selection of reaction conditions. Under Appel conditions (PPh₃/CBr₄), substituted isoxazoles were synthesized from cyclopropyl oximes via a ring-opening and intramolecular cyclization process, whereas by treatment of cyclopropyl oximes with p-toluenesulfonyl chloride in the presence of potassium hydroxide, spiro-fused pyrazolin-5-ones were obtained via tandem ketoxime tosylation and intramolecular cyclization.     

Acid- and Pd(0)-catalyzed ring opening of 1-(1-cycloalkenyl)cyclopropyl sulfonates

We report herein facile acid-catalyzed isomerization of 1-(1'-cycloalkenyl)cyclopropyl sulfonates under mild conditions. The remarkable ease of ring opening is attributed to the presence of a 1'-alkyl substituent. Also included is a palladium-catalyzed ring opening reaction of 1-(1'-cycloalkenyl)cyclopropyl tosylates for convenient preparation of substituted 1,3-dienylamines, which complements previously reported nucleophilic substitution reactions of (1-vinyl)cyclopropyl tosylates.     

Small ring compounds—XXX : Homolytical aromatic substitution and hydrogen abstraction reaction with cyclopropyl radical

Homolytic aromatic substitution and hydrogen abstraction reactions with cyclopropyl radical were carried out to determine the reactivity and ionic character of cyclopropyl radical by examination of the orientation effect, partial rate factor and influence of substituents. By thermal decomposition of biscyclopropaneformyl peroxide in a series of substituted benzenes, the corresponding cyclopropylated benzene derivatives (the mixture of ortho, meta and para isomers) were obtained in moderate yield. In view of the orientation effect and the partial rate factor, the cyclopropyl radical seems to be fairly free from polar effect, and to resemble the phenyl radical more than the common alkyl radical although the cyclopropyl radical has a slightly higher reactivity than the phenyl radical. The relative reactivity of the 2-phenylcyclopropyl radical in the hydrogen abstraction reaction toward the benzylic position of ring-substituted toluenes gave good Hammett's correlation with the slope of + 0·20 suggesting little ionic character in the transition state. This result was in good agreement with the conclusion obtained from homolytic aromatic substitution reaction and with the chemical reactivity to be expected from the non-planar nearly sp²-hybridized conformation of the cyclopropyl radical.     

Electron-impact-induced fragmentation of some isomeric cyclopropyl picolyl and pyridyl ketones

The electron-impact-induced fragmentation of three cyclopropyl picolyl ketones and three cyclopropyl pyridyl ketones has been studied with the aid of deuterium labeling, high resolution mass measurements and metastable mode operation.     

In situ cyclopropanation: a rapid one-pot method for the synthesis of resin bound cyclopropyl phenyl methanones as combinatorial scaffolds

An efficient, high yielding one-pot synthesis of 4-substituted cyclopropyl phenyl methanones bound to RAM and WANG resins has been developed. The resin bound cyclopropyl phenyl methanone served as a combinatorial scaffold for the generation of structurally diverse alicyclic compounds.     

The rates of deprotonation of some p-cyclopropyltoluene derivatives in search for the effect of the conformation of cyclopropyl groups on the stabi

p-Cyclopropyltoluene and 2-cyclopropylmesitylene have been prepared and the rates of base-catalyzed H-D exchange of the benzylic hydrogen atoms, para positioned with respect to the cyclopropyl group, have been compared with those of suitable model compounds. The results are in accord with earlier findings, where a cyclopropyl group exerts more stabilization to the carbanionic centres than do other alkyl groups. The present results suggest that this stabilization is independent of the conformation of the cyclopropyl group (perpendicular or bisected) with respect to the carbanionic centre.     

The behavior of the cyclopropyl phenyl sulfide and phenoxycyclopropane in the reaction with nitrous acid

The behavior of cyclopropyl phenyl sulfide and phenoxycyclopropane in the nitrosation reaction was studied. Cyclopropyl phenyl sulfide was found to convert quantitatively to cyclopropyl phenyl sulfoxide under the action of nitrous acid formed in situ. Under the same conditions, phenoxycyclopropane undergoes transformation to 5-phenoxyisoxasoIine (nitrophenols are formed as byproducts in this reaction).     

Resonance Raman observation of the allyl cation produced after ultraviolet photodissociation of cyclopropyl bromide in acetonitrile solution

We have obtained transient resonance Raman spectra of the [CH₂CHCH₂]⁺ (allyl cation) produced following C-band excitation of cyclopropyl bromide. The experimental resonance Raman spectrum display an overtone progression in the nominal [CCC]⁺ stretch mode and its combination bands with the CH/CH₂ rocking modes. Density functional theory computations were performed to estimate the vibrational frequencies for the allyl cation, the allyl radical, the cyclopropyl radical, the cyclopropyl bromide molecule and the gauche-allyl bromide molecule and compared to the experimental vibrational frequencies. This comparison indicates that the allyl cation can be formed as a product of cyclopropyl bromide photodissociation in acetonitrile solution.     

含环丙基结构的药物研究进展

环丙基的化学结构不同于直链脂肪烃和其他多元脂肪环,在药物分子的设计中经常被使用,具有增强药物的药效、增强代谢稳定性、降低脱靶作用、增强对受体的亲和力、限制多肽的水解作用、增加血脑屏障渗透率、降低血浆清除率以及改善药物的解离度(pK_a)等功效。含有环丙基结构的药物被开发用于治疗呼吸系统疾病、精神障碍类疾病、内分泌和代谢系统疾病、感染性疾病、神经系统疾病、心脑血管疾病以及肿瘤等。本文将对含有环丙基结构药物的研究进展进行综述。     

Cyclopropylmethyl palladium species from carbene migratory insertion: new routes to 1,3-butadienes

Cyclopropylmethyl palladium species can be accessed by Pd-catalyzed reaction of either cyclopropyl N-tosylhydrazone with halide or N-tosylhydrazone with cyclopropyl halide. In both approaches migratory insertion of Pd carbene is the key process. These transformations constitute new approaches toward 1,3-butadiene derivatives.